Sunday, March 30, 2014

NCAA college basketball isn't the only hot competition involving a team from the University of Virginia. UVa Psychology Professor Brian Nosek is one of three founders of Project Implicit, a collaborative nonprofit dedicated to the study of implicit social cognition — how unconscious thoughts and feelings can influence attitudes and behavior.

Prof Nosek is also heavily involved in the Open Science and Replication movements. Along with graduate student Calvin Lai, he led a multinational group of 22 other researchers in a competition to see who could devise the best intervention to reduce racial bias scores on a widely administered implicit test, the race IAT (Lai et al, 2014).

Or does it... ? There have been some vocal critics of the IAT over the years who have questioned what the test actually measures. I'll return to this point later, but for now let's look at the impressive aspects of the new paper.

Performance on the Black-White IAT was compared after 17 brief interventions aimed at changing pro-White bias (and a "faking" condition) relative to a control condition of no pre-test intervention. Participants were over 20,000 non-Black individuals registered at the Project Implicit website, randomized into groups of 300-400. Most of the interventions were tested in four different studies. The contest rules allowed changes to the design between studies. The goal was to lower pro-White bias scores to the point of no preference between Blacks and Whites.

In the IAT, participants classify faces as Black or White and words as good or bad. Some blocks contain only faces or only words. The two critical conditions are shown in the figure above. The stimulus-response mappings are rotated in different blocks to either reinforce stereotypes (bottom) or go against stereotype (top). In the Stereotype condition, participants press the same key when they see White faces or “good” words. They press the other key when they see Black faces or “bad” words. Most White participants (and many African Americans) show a pro-White “preference” or bias, with faster responses when White/good and Black/bad are mapped to the same key (than vice versa).

Conversely, in the Against Stereotype condition, Black faces and positive words are mapped to one key, and White faces and negative words are mapped to the other key. In essence, this induces a response conflict similar to that seen in many classic cognitive psychology tasks such as the color-word Stroop task, e.g. BLUE (say “red”) and the Eriksen flanker task, e.g. ← ← → ← ← (press right button). Slower response times in the IAT conflict conditions has been interpreted as an implicit bias against Black people (Greenwald et al., 2009), although one could argue that executive control abilities play a role here, just as they do in the Stroop task (Siegel et al, 2012).1

The Interventions

The interventions were divided into six different descriptive categories. Although the descriptions were based on existing hypotheses in the literature, they do not imply the operation of any specific psychological mechanism. The interventions had to be brief in length (5 min or less), yield interpretable scores, and have a low attrition rate. See Appendix 1 at the end of this post for a detailed list.

(2) Exposure to counterstereotypical exemplars: assigned to fictional groups with positive Black ingroup members and/or negative White outgroup members; OR think about famous Black people and infamous White people (Interventions #4–8).

(6) Intentional strategies to overcome biases: provide strategies to override or suppress the influence of automatic biases, rather than trying to shift associations directly (Interventions #17 and #18).

To reveal my own a priori biases regarding these descriptive categories, I favor (6) Intentional strategies to overcome biases, which I have writtenabout previously (in 2008). These were interventions #17 Using Implementation Intentions, and #18 Faking the IAT as proposed by Calvin K. Lai, the first author of the manuscript.

Results indicated that nine of the interventions were effective, and nine were ineffective. The interventions that tried to change attitudes (Appeals to egalitarian values), increase empathy or perspective-taking (Engage with others’ perspectives), or elicit an elevated sense of morality (Inducing emotion - Haidt) were completely ineffective.

I note here that the failed interventions all tried to challenge the racially biased attitudes and prejudice purportedly measured by the IAT. These interventions are below the red line in the figure below.

Some of the most effective interventions showed variability across studies, because the parameters were altered between studies (which was allowed). Importantly, some of the interventions included multiple manipulations. The top three, Vivid Counterstereotypic Scenario, Practicing an IAT With Counterstereotypical Exemplars, and Shifting Group Boundaries Through Competition all employed Implementation Intentions in addition to the primary intervention.

What are Implementation Intentions? [in brief, think “Black = good”]

The mechanism connects an environmental cue with the goal intention, making associations between the behavior and the cue more accessible in memory. ... The task gave participants a short tutorial on how to take the IAT and informed them about the tendency for people to exhibit an implicit preference for Whites compared with Blacks. Participants were then asked to commit themselves to an implementation intention by saying to themselves silently, “I definitely want to respond to the Black face by thinking ‘good.’”

On its own, this manipulation was effective in reducing bias scores (p = .032, d = .19). The effect size was enhanced by allowing participants to practice the task before the instructions were given (p = .00037, d = .32). In other words, once subjects were even superficially familiar with the task, being told to think “Black = good” significantly reduced pro-white sentiment (i.e., IAT scores).

This intervention is remarkably similar to my previous anecdotal findings (n=1) for the Human or Alien? test and the Dead or Alive? test. My 2008 results are below. I showed similar effects for the Black-White test and the Women in Science test, but I couldn't find the results for those.

The Neurocritic is Human AND Alien. Coming soon: “Tips for Manipulating the IAT.”

You have completed the study.

Your Result

Your data suggest little to no automatic identification with Human compared to Alien.

If your results, provided above, indicate a stronger identity with alien relative to human, then you are probably an alien.

The Neurocritic is NEITHER Dead NOR Alive. Or both Dead AND Alive. Plus, as promised, today we'll cover “Tips for Manipulating the IAT.”

You have completed the study.

Your Result

Your data suggest little to no automatic identification with Alive compared to Dead.

Your results, summarized above, are an implicit indicator of whether you are alive or dead. Implicit measures are superior to self-report because the latter is notoriously unreliable. People may report being alive because social pressures suggest that it is more desirable to be alive. Also, people may not have introspective access to their animate-status, making such self-report untrustworthy.

Super Secret Tip for Manipulating the IAT

My “faking” strategy was simple, and relied on neither deliberate slowing of response times nor a long-standing affiliation with aliens. When SELF and ALIEN were mapped to the same key, I merely said to myself, “I'm an alien.” This strategy was transient, applied only when those stimulus-response mappings were the same, not when SELF and ALIEN were mapped to different keys. I used the same strategy for the Dead or Alive IAT. In both cases, I responded as quickly and as accurately as possible.

Here, what I'm calling “faking” is the Using Implementation Intentions instructions (and not the Faking the IAT intervention of Lai et al, 2014). Again, the top three contest winners combined this strategic feature with another manipulation, as noted by the authors:

The three most effective interventions appear to leverage multiple mechanisms to increase their impact on implicit preferences... The most effective intervention, Vivid Counterstereotypic Scenario, involved the participant as the subject of the story, had the participant imagine his- or herself under a highly threatening life-or-death situation, exposed participants to counterstereotypical exemplars (malevolent White villain, dashing Black hero), and provided strategies to overcome bias (goal intentions to associate good with Black and bad with White) to reduce implicit preferences.

This vivid intervention is illustrated by using a TV example in Appendix 2. [Note: participants in the actual experiment read a story; they did not watch an episode of Criminal Minds.] The strategy was receiving the instruction that “the task following the story (i.e., the race IAT) was supposed to affirm the associations: White = Bad, Black = Good.”

The conclusion I draw from this impressive project is that performance on the IAT is subject to strategic control, supporting the notion that the IAT is not a pure measure of implicit attitudes. Even a brief training session is sufficient to reduce (or reverse) stereotypical preferences and associations that are supposed to be unconscious in nature (also see Hu et al., 2012; Siegel et al, 2012).

1 Another common paradigm in cognitive psychology, semantic priming, can explain a goodly portion of the effect as well. In one study, the bias shown in IAT scores was based on statistical co-occurrence of words and concepts in the ambient culture and not on prejudiced attitudes. A discussion of those findings is beyond the scope of this post.

...participants read an evocative story told in second-person narrative in which a White man assaults the participant and a Black man rescues the participant ( “With sadistic pleasure, he beats you again and again. First to the body, then to the head. You fight to keep your eyes open and your hands up. The last things you remember are the faint smells of alcohol and chewing tobacco and his wicked grin”).

Sunday, March 23, 2014

In 1987, over 100 Canadians became ill after eating cultivated mussels from Prince Edward Island. Symptoms included the typical gastrointestinal issues, but serious neurological findings such as disorientation, confusion, and memory loss were also observed (Perl et al., 1990). In the worst cases, the patients developed seizures or went into coma. Three elderly people died. The cognitive changes were persistent, and had not resolved within a two year follow-up.

The toxin was identified as domoic acid, which received the well-deserved moniker of Amnesiac Shellfish Poison. Domoic acid is a potent excitatory amino acid that activates kainate and AMPA receptors, the binding sites for the ubiquitous excitatory neurotransmitter glutamate. It acts as an excitotoxin by overstimulating these receptors, causing a flood of calcium ions into the cells. Particularly vulnerable are neurons in medial temporal lobe structures such as the amygdala and the hippocampus, which is critical for memory.

Postmortem examination of four brains revealed hippocampal pathology that could account for the clinically significant anterograde amnesia seen in other (still living) patients (Teitelbaum et al., 1990). The pattern of neuronal loss was consistent with the damage observed in kainic acid animal models of epilepsy.

Fig. 3 (modified from Teitelbaum et al., 1990). Panel A: Section of hippocampus from a patient who died 24 days after mussel-induced intoxication, showing severe loss of neurons in all fields except CA2 (arrow), and tissue collapse is evident in part of field CA1 (double arrow). Panel B: Control Subject.

What was the source of the Amnesiac Shellfish Poison that had accumulated in the mussels? A "red tide" of phytoplankton created a harmful algal bloom that produced domoic acid, which accumulates not only in shellfish but also in fish such as anchovies and sardines.
This is where the California sea lions make their noisy entrance...

The Marine Mammal Center in Sausalito, California rescues and rehabilitates sick, stranded, and malnourished marine mammals, including seals, sea lions, and cetaceans. An up-to-date list of their current patients is available here. They are the premiere institution for the diagnosis, treatment, and scientific study of domoic acid toxicity in California sea lions:

The Marine Mammal Center was the first group to definitively diagnose DA posioning in marine mammals because of a large outbreak in California sea lions in 1998. In September 2004, the Center received a grant from the Oceans and Human Health Initiative to study the long term effects of domoic acid in sea lions. This project studied the impact of DA on health, survival, and reproduction. Part of this project focused on the neurological effects of DA. Effects were evaluated using magnetic resonance imaging (MRI), cognitive behavior tests (how the animal behaves), and histopathology (tissue samples from dead animals).

Their website on the topic is highly recommended, and contains links to published papers such as Magnetic resonance imaging quality and volumes of brain structures from live and postmortem imaging of California sea lions with clinical signs of domoic acid toxicosis [PDF].

Most recently, a team of researchers from Stanford University collaborated with the Marine Mammal Center to conduct a detailed neuropathological investigation of the brains of sea lions who suffered from seizures due to domoic acid toxicity (Buckmaster et al., 2014). Unfortunately, this is not an uncommon occurrence, since the current census of pinniped patients includes five sea lions diagnosed with acute domoic acid toxicity. In the chronic state, the animals can experience recurrent seizures, leading to a failure to thrive and poor prognosis. The authors hypothesize that the animals develop temporal lobe epilepsy, which can serve as an unfortunate accidental model of temporal lobe epilepsy in humans.

The researchers examined the brains of 14 domoic acid-exposed (DA) animals and 9 control animals. Five of the affected sea lions were admitted in status epilepticus, a state of continual seizure that can cause severe brain damage and even death. The study expanded on earlier work by using stereological methods to obtain an unbiased estimate of the total number of neurons in each hippocampus (left and right hemispheres).

In control sea lions, Buckmaster and colleagues (2014) estimated that each hippocampus contains over 6 million neurons! For the comparative hippocampal anatomy aficionados, sea lions had a relatively small proportion of neurons in the dentate gyrus granule cell layer relative to other mammals (i.e., macaque monkeys, squirrel monkeys, dogs, rats, and mice), and the granule cell layer was thinner than in other species.

Importantly, the authors observed significant neuronal loss in the DA-exposed animals, with substantial variation across the hippocampal subfields (see Fig. 3). And interestingly, the damage was unilateral in most cases: the left hippocampus in four, the right hippocampus in seven, and bilaterally in only three.

Fig. 1 (modified from Buckmaster et al., 2014). Nissl-stained cell bodies in the hippocampi from (A) control and (B-D) chronic domoic acid sea lions. Note the increasing levels of neuron loss in the three chronic DA cases. All were admitted in status epilepticus with DA toxicity. In (A), lines indicate border between the hilus (h) and CA3 field. g, granule cell.

In addition, the authors compared the pattern of neuronal loss in sea lions to that observed in human patients with temporal lobe epilepsy, using tissue obtained at autopsy or after temporal lobe resection (for seizure control):

Substantial neuron loss was evident in all hippocampal subfields of patients with temporal lobe epilepsy and chronic DA sea lions compared with controls (Fig. 3B). In sea lions neuron loss was more severe in the hilus, CA3, and CA2 subfields compared with humans. In humans neuron loss was more severe in CA1. Sea lions and humans displayed similar levels of granule cell loss.

As we saw in the earlier cases of Amnesiac Shellfish Poisoning in Canada, the CA1 region of the hippocampus was especially vulnerable, and this is also true in cases of hypoxia or anoxia. However, it's notable that significant neuron loss was observed throughout the hippocampus.

Why the difference from sea lion CA1? The reasons are unclear. Nonetheless, when examining the brain as a whole, it is remarkable that the hippocampus shows such qualitatively similar pathology in sea lions andhumans poisoned by domoic acid, and humans with temporal lobe epilepsy. The authors speculate that the misfortune of chronic DA sea lions may yield an opportunity to test new anti-seizure treatments, for the benefit of both marine and terrestrial mammals.

Wednesday, March 05, 2014

The dissociative anesthetic and ravey club drug ketamine has been hailed as a possible “miracle” cure for depression. In contrast to the delayed action of standard antidepressants such as SSRIs, the uplifting effects of Special K are noticeable within an hour. “Experimental Medication Kicks Depression in Hours Instead of Weeks,” says the National Institute of Mental Health. NIMH has been bullish on ketamine for years now. Prominent researchers Duman and Aghajanian called it the “the most important discovery in half a century” in a recent Science review.

But in 2010, I pondered whether this use of ketamine was entirely positive:

Now, in the latest issue of the American Journal of Psychiatry, Dr. Alan F. Schatzberg of Stanford University School of Medicine has a commentary entitled, A Word to the Wise About Ketamine. He first acknowledges the excitement about acute ketamine for refractory depression, then raises several cautionary notes and warns:

“This unbridled enthusiasm needs to be tempered by a more rational and guarded perspective.”

He notes that the drug is administered off-label in free-standing private psychiatry clinics without regulation by the FDA. Some leading proponents have advocated for strictly inpatient use, but that cat is already out of the bag.

Another potential issue is abuse liability. The antidepressant effects of ketamine are short-lived (less than a week), which means that repeated infusions are required. The published literature suggests a relatively safe profile over two weeks in a hospital setting, but patients at commercial clinics are unlikely to be monitored as closely.

The commentary also suggests that “We Need To Know More About the Mechanism of Action of the Mood-Elevating Effects” — but that is true of all drugs with antidepressant properties.

Without more data on what ketamine can do clinically, except to produce brief euphoriant effects after acute administration, and knowing it can be a drug of abuse, it is difficult to argue that patients should receive an acute trial of ketamine for refractory depression. ... The recent ketamine studies are exciting, and they open up important avenues for investigation that should be supported; however, until we know more, clinicians should be wary about embarking on a slippery ketamine slope.

However, in the midst of all this naysaying, it's important to note that Dr. Schatzberg has extensive ties to the pharmaceutical and biotech industries. He receives consulting fees from 19 different companies and has equity in 16 different companies, including one for which he is a co-founder. Ketamine of course is not under patent and is cheap to purchase. Perhaps not coincidentally, he does not receive fees from AstraZeneca, which (until recently) was developing a “low-trapping” NMDA antagonist that does not cause the hallucinogenic effects of ketamine (AZD6765, aka lanicemine).

In the past, I have suggested that short-term use for immediate relief of life-threatening symptoms (i.e. suicidal ideation) or end-of-life depression seem to be the best indications. Neuroskeptic has argued for the use of an active placebo condition (i.e, a non-dissociative comparison drug) in clinical trials, which has happened only rarely (Murrough et al., 2013), and for better assessment of dissociative behavioral effects.

At this point, the long-term ramifications of ketamine use for treatment-resistent depression remain to be seen...

In a future post I'll investigate the potential side effects in more detail.

Declaration

I have no financial conflicts to declare. But if some company wants to employ a critic for some bizarre reason, I'll take this under advisement.

About Me

Born in West Virginia in 1980, The Neurocritic embarked upon a roadtrip across America at the age of thirteen with his mother. She abandoned him when they reached San Francisco and The Neurocritic descended into a spiral of drug abuse and prostitution. At fifteen, The Neurocritic's psychiatrist encouraged him to start writing as a form of therapy.